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Biomedical subjects

D A Ginsberg

Publications and source records attributed to D A Ginsberg.

At least 19 recordsLinked to original sources

Posterior vaginal wall prolapse: transvaginal repair of pelvic floor relaxation, rectocele, and perineal laxity.

PURPOSE: Posterior vaginal wall laxity is one manifestation of pelvic organ prolapse in the female. Recognition and repair of the inherent anatomical defects present in this condition are essential in order to ensure a satisfactory surgical result. METHODS AND MATERIALS: A successful operation for posterior vaginal wall prolapse will often involve repair of three discreet abnormalities in support of the posterior vaginal wall, including the pelvic floor, posterior vaginal wall fascia, and perineal musculature. An overaggressive repair is to be assiduously avoided as this can lead to excessive narrowing of the vaginal canal and considerable postoperative symptoms including dyspareunia. RESULTS: Durable restoration of anatomical support can be achieved in >80% of cases. Functional results in symptomatic patients undergoing posterior vaginal wall prolapse repair do not appear to be as successful in some areas. CONCLUSIONS: Successful surgical repair of posterior vaginal wall prolapse requires a thorough understanding of the anatomy and pathophysiology involved in this condition. A careful anatomical dissection and reconstruction will result in successful anatomical repair in the majority of patients with minimal morbidity.

Female↗

4-Defect repair of grade 4 cystocele.

PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe deficiencies of vesicourethral support. We describe this technique used during pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period 130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele using the 4-defect repair technique. Cystocele repair had been performed in 60 patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost incision" is used in the vaginal wall to facilitate separation of the wall from underlying perivesical fascia, entry into the retropubic space, and exposure of the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4 polypropylene sutures are used to provide an anterior vaginal wall sling which is modified to incorporate perivesical fascia and cardinal ligaments. Central defect repair is achieved by approximation of the cardinal ligaments and midline plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112 patients were available for followup which ranged from 6 to 42 months (mean 21). Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94 patients (83%), including rectocele repair in 81, hysterectomy in 22 and enterocele repair in 31. Of the patients 92% had excellent objective and subjective results for anatomical cystocele repair. Of the patients with preoperative stress urinary incontinence 90% had excellent or good subjective results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4-defect repair technique relies on anatomical restoration of 4 distinct deficiencies of pelvic support and is highly effective for relief of symptoms of grade 4 cystocele.

Adult↗

Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer.

BACKGROUND: Altered expression of p53 protein is an important predictor of progression in bladder cancer. The action of p53 on cell cycle regulation is mediated, in part, through expression of the cyclin-dependent kinase inhibitor p21WAF/CIP1 (p21). Loss of p21 expression may, therefore, contribute to tumor progression. We sought to determine the relationship between p21 expression in bladder cancer and disease progression. METHODS: Tumor specimens were obtained from 242 patients who underwent cystectomy for bladder cancer. Median follow-up was 8.5 years (range, 0.1-11.8 years). Nuclear p21 status was determined by immunohistochemistry and was then analyzed in relationship to the probability of tumor recurrence, overall survival, and tumor p53 status. Reported P values are two-sided. RESULTS: Nuclear p21 expression was detected in the tumors of 156 (64%) of the 242 patients. Patients with p21-positive tumors had a decreased probability of tumor recurrence (P<.00001) and an increased probability of overall survival (P<.00001) in comparison with patients with p21-negative tumors. In a multivariable analysis, p21 expression was an independent predictor of tumor recurrence (P = .0017) and of survival (P = .006) when assessed with tumor grade, tumor stage, lymph node status, and p53 status. p21 expression was associated with p53 status (P<.001); 56% of tumors with p53 alterations showed loss of p21 expression, whereas 79% of tumors expressing wild-type p53 were p21 positive. Patients with p53-altered/p21-negative tumors demonstrated a higher rate of recurrence and worse survival compared with those with p53-altered/p21-positive tumors (P<.0001). Patients with 53-altered/p21-positive tumors demonstrated a similar rate of recurrence and survival as those with p53-wild type tumors. CONCLUSION: Loss of p21 expression is a statistically significant and independent predictor of bladder cancer progression. Maintenance of p21 expression appears to abrogate the deleterious effects of p53 alterations on bladder cancer progression.

Aged↗

Prognostic markers in bladder cancer: a contemporary review of the literature.

PURPOSE: We provide a contemporary review of bladder tumor markers and summarize their role as prognostic indicators. MATERIALS AND METHODS: A comprehensive review of the literature on prognostic markers for transitional cell carcinoma of the bladder was performed. RESULTS: Intense research efforts are being made to identify and characterize better various bladder cancers and their true biological potential. The need to predict which superficial tumors will recur or progress and which invasive tumors will metastasize has led to the identification of a variety of potential prognostic markers. Blood group antigens, tumor associated antigens, proliferating antigens, oncogenes, peptide growth factors and their receptors, cell adhesion molecules, tumor angiogenesis and angiogenesis inhibitors, and cell cycle regulatory proteins have recently been identified. The potential clinical applications of these tumor markers are under active investigation. Recent attention has focused on which tumor markers may predict the responsiveness of a particular bladder cancer to systemic chemotherapy. CONCLUSIONS: At present conventional histopathological evaluation of bladder cancer (tumor grade and stage) cannot predict accurately the behavior of most bladder tumors. With a better understanding of the cell cycle, and cell to cell and cell to extracellular matrix interactions as well as improved diagnostic techniques (immunohistochemistry), progress is being made to identify and characterize other potential prognostic markers for transitional cell carcinoma of the bladder. The ultimate goal is to develop reliable prognostic markers that will accurately predict not only the course but also the response of a tumor to therapy. This information may then be used to dictate more aggressive treatment for tumors that are likely to progress and less aggressive treatment for those that are unlikely to progress. In the future these biological markers may also be used in gene therapy for the treatment of bladder cancer.

Antigens, Neoplasm↗

A serous lined antireflux valve: in vivo fluorourodynamic evaluation of antireflux continence mechanism.

PURPOSE: We evaluate the fluoroscopic and urodynamic performance of a new serosal lined antireflux continence valve (T pouch valve) using an in vivo animal model. MATERIALS AND METHODS: Intestinal reservoirs were constructed using an in vivo pig model. Multiple serosal lined valves of varying diameters and tunnel lengths were evaluated in the acute (immediately after construction) and chronic (4 weeks postoperatively) settings. Video fluorourodynamic evaluations were performed to identify valve leak point pressures and optimal tunnel length-to-luminal diameter ratios. RESULTS: Four serosal lined valves tapered to a diameter of 18 and 30F in 1 and 2 cm. tunnels were evaluated. Immediately following construction of the valves no leakage was observed during reservoir filling (maximal pressure 50 cm. water) or external compression maneuvers to simulate a Valsalva maneuver (maximal intra-reservoir pressure 100 cm. water). Identical fluorourodynamic studies performed after a 4-week recuperation demonstrated leakage through the 30F, 1 cm. tunnel valve during reservoir filling (intra-reservoir pressure 19 cm. water). Increasing the tunnel length of the 30F system to 2 cm. (tunnel length-to-luminal diameter ratio 2:1) eliminated all evidence of valve leakage up to a maximal intra-reservoir pressure of 100 cm. water. CONCLUSIONS: These studies demonstrate the urodynamic characteristics of a new serosal lined valve. This easily constructed mechanism serves as a reliable antireflux (afferent) or continence (efferent) system.

Animals↗

The T pouch: an orthotopic ileal neobladder incorporating a serosal lined ileal antireflux technique.

PURPOSE: At our institution the Kock ileal neobladder has been the primary form of urinary diversion after cystectomy. The few associated complications are primarily related to the intussuscepted antireflux afferent limb, including stones, stenosis and extussusception of the afferent nipple. We present a novel orthotopic ileal neobladder, the T pouch, with an innovative antireflux technique designed to prevent complications of the intussuscepted afferent nipple. MATERIAL AND METHODS: From November 1996 through August 1997, 40 patients an average of 67 years old underwent construction of an orthotopic ileal neobladder (T pouch). Mean followup is 10.5 months (range 8 to 14). The T pouch incorporates an antireflux mechanism using a serosal lined ileal tunnel technique. Urinary reflux is prevented without ileal intussusception and with complete preservation of the blood supply to the afferent ileal segment. Followup in all cases includes clinical and functional results, and radiographic evaluation of the urinary reservoir and upper urinary tracts. RESULTS: One perioperative death (2.5%) and 5 early complications (12.5%) were unrelated to urinary diversion. There have been no late complications. All T pouch reservoirs had excellent capacity without evidence of urinary reflux. The upper urinary tracts remain unchanged or improved in all patients. CONCLUSIONS: The T pouch is an orthotopic ileal neobladder that incorporates an effective, innovative antireflux mechanism created by a serosal lined ileal tunnel. Early clinical and functional results of this type of urinary diversion have been excellent. Furthermore, we suspect that this antireflux technique may eliminate the complications associated with an intussuscepted afferent nipple and maintain an effective antireflux mechanism.

Adult↗

Vaginal evisceration.

Vaginal evisceration is a rare complication of an enterocele. We report a patient who presented with spontaneous evisceration per vagina secondary to erosion through an attenuated vaginal wall. This resulted in a strangulated hernia requiring bowel resection and enterocele repair. This patient is discussed as are the risk factors and management options for patients with vaginal evisceration.

Female↗

Prospective pathologic analysis of female cystectomy specimens: risk factors for orthotopic diversion in women.

OBJECTIVES: To prospectively evaluate our previously established pathologic risk factors in women undergoing cystectomy for bladder cancer and to determine if these criteria identify appropriate female candidates for orthotopic diversion. METHODS: Prospective pathologic evaluation was performed on 71 consecutive female cystectomy specimens removed for primary transitional cell carcinoma of the bladder. The histologic grade, pathologic stage, presence of carcinoma in situ, number, and location of tumors were determined. In addition, final pathologic analysis of the bladder neck and proximal urethra was performed and compared with the intraoperative frozen-section analysis of the distal margin (proximal urethra). RESULTS: Tumor at the bladder neck and proximal urethra was seen in 14 (19%) and 5 (7%) cystectomy specimens, respectively. Bladder neck tumor involvement was found to be the most significant risk factor for tumor involving the urethra (P <0.001). All patients with urethral tumors demonstrated concomitant bladder neck tumors. However, more than 60% of patients with bladder neck tumors had a normal (tumor-free) proximal urethra. Furthermore, no patient with a normal bladder neck demonstrated tumor involvement of the urethra. Intraoperative frozen-section analysis of the distal surgical margin was performed on 47 patients: 45 without evidence of tumor and 2 patients with urethral tumor involvement. In all cases, the intraoperative frozen-section analysis was correctly confirmed by final permanent section. CONCLUSIONS: We prospectively demonstrate that bladder neck tumor involvement is a significant risk factor for urethral tumor involvement in women. However, despite bladder neck tumor involvement, a number of women undergoing cystectomy for bladder cancer have a normal urethra and may be candidates for orthotopic diversion. Furthermore, our data demonstrate that intraoperative frozen-section analysis of the distal surgical margin accurately and reliably evaluates the proximal urethra and currently determines which patients undergo orthotopic diversion at our institution.

Adult↗

Posthysterectomy vaginal cuff fistula: diagnosis and management of an unusual cause of "incontinence".

OBJECTIVES: Connection between the vaginal cuff and the peritoneal cavity after hysterectomy is a rare event that can mimic urinary incontinence. The appropriate evaluation and treatment of these patients is discussed. METHODS: Five patients underwent excision of the vaginal cuff during a 12-month period. All of these patients had a negative workup for urinary incontinence, except for 1 patient who also had stress incontinence and required a vaginal wall sling at the time of cuff excision. RESULTS: All 5 patients are presently free of excess vaginal drainage or significantly improved, with a mean follow-up of 6 months. One patient developed stress incontinence after cuff excision and later required a vaginal wall sling. There have been no perioperative complications and no evidence of recurrent fistula. CONCLUSIONS: Fistula of the vaginal cuff is a diagnosis of exclusion after urinary incontinence has been ruled out. A high index of suspicion is often required to make the diagnosis because these patients often present with symptoms highly suggestive of urinary leakage. Fistula of the vaginal cuff is successfully treated with excision of the vaginal cuff and the fistulous tract (if identified), with minimal morbidity.

Adult↗

Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression.

BACKGROUND: Thrombospondin-1 (TSP) is a 430-kd glycoprotein that is an important component of the extracellular matrix and is known to be a potent inhibitor of angiogenesis (i.e., formation of new blood vessels) both in vitro and in vivo. Several reports suggest that TSP possesses tumor suppressor function, possibly through its ability to inhibit tumor neovascularization. It has recently been shown that TSP expression is enhanced by the product of the p53 gene (also known as TP53). PURPOSE: We examined the role of TSP expression in tumor recurrence and overall survival in patients with invasive bladder cancer. We also examined the relationship between alterations in p53 protein expression, TSP expression, and tumor angiogenesis. METHODS: Tumors from 163 patients (with a median follow-up of 7.7 years) who underwent radical cystectomy for invasive transitional cell carcinoma of the bladder (63 patients with organ-confined disease and no lymph node involvement, 48 patients with extravesical extension of the disease and no lymph node involvement, and 52 patients with metastasis to regional lymph nodes) were examined for TSP expression by immunohistochemistry, utilizing monoclonal antibody MA-II, which recognizes an epitope in the amino-terminal region of TSP. For each tumor, microvessel density counts and p53 protein expression status (via immunohistochemistry) were also determined. TSP expression was graded as low, moderate, or high without knowledge of clinical outcome, p53 status, and microvessel density count; tumors with moderate and high TSP levels were considered as one group. Groups of patients were compared by Kaplan-Meier product limit estimates of overall survival, the complement of cumulative incidence curves for recurrence-free survival, and the stratified logrank test. Reported P values are two-sided. RESULTS: TSP expression was significantly associated with disease recurrence (P = .009) and overall survival (P = .023). Patients with low TSP expression exhibited increased recurrence rates and decreased overall survival. TSP expression was an independent predictor of disease recurrence (P = .002) and overall survival (P = .01) after stratifying for tumor stage, lymph node status, and histologic grade, but it was not independent of p53 status. TSP expression was significantly associated with p53 expression status (P = .001) and microvessel density counts (P = .001). Tumors with p53 alterations were significantly more likely to demonstrate low TSP expression, and tumors with low TSP expression were significantly more likely to demonstrate high microvessel density counts. Results of an analysis of variance were compatible with the hypothesis that p53 affects tumor angiogenesis by regulating the level of TSP expression. CONCLUSIONS AND IMPLICATIONS: These data support the concept that TSP may possess a tumor-inhibitory function. TSP may act, in part, through the regulation of tumor neovascularity. These results may also provide insight into one mechanism by which p53 exerts its tumor suppressor effects, i.e., through the control of tumor angiogenesis.

Adult↗

The UCLA surgical approach to sphincteric incontinence in women.

Stress urinary incontinence (SUI) in the female may be treated by a variety of non-surgical and surgical therapies. However, once the patient has chosen to undergo operative repair the ideal procedure is based on three considerations: the degree of anterior vaginal wall prolapse, the degree of incontinence and associated anatomic abnormalities requiring surgical repair. In the vast majority of cases vaginal wall sling is our procedure of choice for the surgical treatment of SUI in the female. Vaginal wall sling is based on sound anatomic principles, may be performed as an outpatient procedure and is equally efficacious for the treatment of SUI due to anatomic incontinence (urethral hypermobility) and intrinsic sphincter deficiency. Since vaginal wall sling is performed through a transvaginal approach, other associated manifestations of pelvic floor prolapse such as rectocele can be addressed and repaired simultaneously. When necessary the vaginal wall sling can be easily modified to repair large grade cystoceles.

Female↗

Horseshoe kidney with a retrocaval ureter.

Horseshoe kidney and retrocaval ureter are two uncommon congenital anomalies of the genitourinary system that have rarely been reported to occur in the same patient. In each case previously reported, the isthmus of the horseshoe was positioned posterior to the inferior vena cava and anterior to the aorta. In no case was the diagnosis of both anomalies made preoperatively. We report a case of simultaneous horseshoe kidney and retrocaval ureter diagnosed by preoperative imaging studies and discuss the diagnostic evaluation and surgical management of this rare entity.

Abnormalities, Multiple↗

A method for intraoperative adjustment of sling tension: prevention of outlet obstruction during vaginal wall sling.

OBJECTIVES: To describe a simple, yet effective method of adjusting intraoperative tension on the suspending sutures of a vaginal wall sling placed for treatment of stress urinary incontinence (SUI) in the female patient. METHODS: A cystoscope sheath is placed per urethra and inclined to approximately 20 degrees to 30 degrees relative to horizontal. The suspension sutures are tied down directly onto the rectus fascia but do not indent it. The sheath should easily rotate in the vertical plane within the urethral lumen, maintaining elastic mobility as the sutures are tied. RESULTS: On review of the first 160 patients who have undergone vaginal wall sling using this technique of tension adjustment, no patient has had unexpected permanent urinary retention. Preoperative urgency incontinence has remained in 10 patients (less than 7%) postoperatively; 11 patients (6.8%) have had recurrent SUI during follow-up. CONCLUSIONS: Proper adjustment of suture tension during performance of a sling procedure for SUI is critical in preventing urethral obstruction. The technique described is simple, objective, reproducible, and highly effective.

Cystoscopy↗

Orthotopic lower urinary tract reconstruction in women using the Kock ileal neobladder: updated experience in 34 patients.

PURPOSE: Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients. MATERIALS AND METHODS: Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70). RESULTS: There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming. CONCLUSIONS: The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

Adult↗